ArticleBiochemistry2013
Some ligands enhance the efflux of other ligands by the Escherichia coli multidrug pump AcrB.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Computer Simulations of Multidrug Efflux Pumps of the Resistance-Nodulation-Cell Division Superfamily.Methods in molecular biology (Clifton, N.J.) · 2026Article
- AcrAB-TolC, a major efflux pump in Gram negative bacteria: toward understanding its operation mechanism.BMB reports · 2023Review
- Tripartite efflux pumps of the RND superfamily: what did we learn from computational studies?Microbiology (Reading, England) · 2023Review
- A framework for dissecting affinities of multidrug efflux transporter AcrB to fluoroquinolones.Communications biology · 2022Article
- Structural Insights into Transporter-Mediated Drug Resistance in Infectious Diseases.Journal of molecular biology · 2021Review
- Allosteric drug transport mechanism of multidrug transporter AcrB.Nature communications · 2021Article
- Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race against Time.Antibiotics (Basel, Switzerland) · 2021Review
- Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria.Chemical reviews · 2021Review
- Article
- Chlorpromazine and Amitriptyline Are Substrates and Inhibitors of the AcrB Multidrug Efflux Pump.mBio · 2020Article
- Discovery of multidrug efflux pump inhibitors with a novel chemical scaffold.Biochimica et biophysica acta. General subjects · 2020Article
- Deletion of the major Escherichia coli multidrug transporter AcrB reveals transporter plasticity and redundancy in bacterial cells.PloS one · 2019Article
- Multidrug efflux pumps: structure, function and regulation.Nature reviews. Microbiology · 2018Review
- Effect of site-directed mutations in multidrug efflux pump AcrB examined by quantitative efflux assays.Biochemical and biophysical research communications · 2016Article
- Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions.Antibiotics (Basel, Switzerland) · 2016Review
- Aminoacyl β-naphthylamides as substrates and modulators of AcrB multidrug efflux pump.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Reversal of the Drug Binding Pocket Defects of the AcrB Multidrug Efflux Pump Protein of Escherichia coli.Journal of bacteriology · 2015Article
- The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria.Clinical microbiology reviews · 2015Review
- AcrB drug-binding pocket substitution confers clinically relevant resistance and altered substrate specificity.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- The ins and outs of RND efflux pumps in Escherichia coli.Frontiers in microbiology · 2015Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
By measuring quantitatively the active efflux of cephalosporins by the RND (resistance-nodulation-division) family efflux pump AcrB in intact cells of Escherichia coli, we found that the simultaneous presence of another substrate, such as chloramphenicol, benzene, cyclohexane, or Arg β-naphthilamide, significantly enhanced the extrusion of cephalosporins. The stimulation occurred also in a strain expressing the covalently linked trimer of AcrB, and thus cannot be ascribed to the enhanced assembly of the trimer from AcrB monomers. When Val139 of AcrB was changed into Phe, the stimulation by benzene was found to occur at much lower concentration of the solvent. A plausible explanation of these observations is that the AcrB pump is constructed to pump out very rapidly the solvent or chloramphenicol molecules, and thus the efflux of cephalosporins, which presumably bind to a different subsite within the large binding pocket of AcrB, can become facilitated. Computer simulations of ligand binding to AcrB, both by docking and by molecular dynamics simulations, produced results supporting and extending this hypothesis. Benzene and the cephalosporin nitrocefin can bind simultaneously to the distal binding pocket of AcrB, both in the wild type and in the V139F variant. Interestingly, while the binding position and strength of benzene are almost unaffected by the presence of nitrocefin, this latter substrate is significantly displaced toward the exit gate in both wild type and mutant transporter in the presence of benzene. Additionally, the cephalosporin efflux may be enhanced by the binding of solvents (sometimes to the cephalosporin-free protomer), which could accelerate AcrB conformational changes necessary for substrate extrusion.
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